PIWIL4 and piRNAs in RSV Infection

项目总结/摘要 急性呼吸道感染是全世界儿童发病和死亡的主要原因。 呼吸道合胞病毒（RSV）是儿童、老年人和老年人下呼吸道感染的主要原因， 免疫功能低下的患者，以及哮喘急性发作。没有有效的RSV治疗或疫苗 是目前可用的，和许多基本的问题，关于RSV诱导的肺 疾病尚未得到解答。已经发现小的非编码RNA（sncRNA）调节许多 细胞过程，包括宿主-病毒相互作用。RSV感染可显著改变表达谱 和几种类型的sncRNA，如miRNA和tRFs，已被证明发挥作用， 在RSV复制和病毒诱导的宿主应答中起重要作用。在最近的研究中，我们发现RSV 感染改变了piwiRNA（piRNA）的表达，piRNA是最大的一类sncRNA分子 在动物细胞中表达。虽然piRNA的作用最初仅限于性腺发育，但最近的研究表明， 研究已经鉴定了来自多个器官和细胞类型的piRNA的特异性表达谱，并且不同的piRNA表达谱是不同的。 谱已经与几种疾病相关，包括各种类型的癌症、心血管疾病、糖尿病、糖尿 疾病、自身免疫和神经变性病症。令人惊讶的是，几乎没有人知道 病毒感染背景下的皮尔纳生成/功能和PIWI蛋白。识别模式和 人类sncRNA产生的细节极大地帮助理解它们如何调节宿主 在病毒感染的情况下，拟议研究的结果将导致新的知识 关于piRNA在RSV诱导的细胞应答中的作用， 用于疾病诊断和预后的靶标和/或生物标志物。

PROJECT SUMMARY/ABSTRACT Acute respiratory tract infections are a leading cause of morbidity and mortality in children worldwide. Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, elderly and immunocompromised patients, as well as of asthma exacerbations. No effective treatment or vaccine for RSV is currently available, and many fundamental questions regarding the pathogenesis of RSV-induced lung disease have yet to be answered. Small non-coding RNAs (sncRNAs) have been found to regulate many cellular processes, including host-virus interactions. RSV infection can significantly alter the expression profile of host sncRNAs, and several types of sncRNAs, such as miRNA and tRFs, have been shown to play a significant role in RSV replication and virus-induced host responses. In recent studies, we found that RSV infection alters the expression of piwi RNAs, (piRNAs), one of the largest classes of sncRNA molecules expressed in animal cells. Although the role of piRNAs was initially confined to gonad development, recent studies have identified specific expression profile of piRNAs from multiple organs and cell types, and different profiles have been associated with several diseases, including various types of cancers, cardiovascular diseases, autoimmune and neurodegenerative disorders. Surprisingly, almost nothing is known regarding piRNA generation/function and PIWI proteins in the context of viral infections. Identification of patterns and details of human sncRNAs generation has significantly helped understanding how they modulate host responses in the context of viral infections. The outcome of the proposed studies will lead to new knowledge regarding the role of piRNAs in RSV-induced cellular responses, potentially identifying novel therapeutic targets and/or bio-markers for disease diagnosis and prognosis.